TY - JOUR T1 - Clinical efficacy of leflunomide in primary Sjögren's syndrome is associated with regulation of T-cell activity and upregulation of IL-7 receptor α expression JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 1934 LP - 1941 DO - 10.1136/annrheumdis-2011-201026 VL - 71 IS - 12 AU - Angela Bikker AU - Jan-Maarten van Woerkom AU - Aike A Kruize AU - Kim M G van der Wurff-Jacobs AU - Johannes W J Bijlsma AU - Floris P J G Lafeber AU - Joel A G van Roon Y1 - 2012/12/01 UR - http://ard.bmj.com/content/71/12/1934.abstract N2 - Objectives To investigate whether the immunomodulatory capacities of leflunomide are associated with clinical efficacy in the treatment of primary Sjögren's syndrome (SS) in a phase II pilot study. Methods Peripheral blood mononuclear cells from 13 primary SS patients were obtained at baseline and after 24 weeks of leflunomide treatment. Ex-vivo production of interleukin (IL) 1β and tumour necrosis factor α (TNFα) and of interferon (IFN), IL-4, as well as TNFα ELISA measured production on T-cell and monocyte stimulation. In addition, the authors investigated the ability of leflunomide to influence systemic levels of inflammatory cytokines, as well as T-cell activation markers and the expression of IL-7 receptor α by flow cytometry. Correlations between changes in cytokine levels and changes in clinical response parameters were studied. Results Ex-vivo production of IL-1β and TNFα was decreased at 24 weeks in the whole patient group, whereas IFN and IL-4 production were not significantly changed. However, a significant decrease in T-cell-stimulated IFN and TNFα production was observed in clinical responders, but not in non-responders. Moreover, significant correlations were found between increased sialometry values and decreased IFN and TNFα production. In addition, leflunomide reduced levels of inflammatory serum cytokines and CD40L expression, whereas it upregulated IL-7Rα expression on CD4 T cells with persistent serum IL-7 concentrations. Conclusions Leflunomide treatment suppressed cytokine release from circulating immune cells. Inhibition of T-helper 1 cell cytokine production was related to clinical efficacy. This suggests that selective T-cell targeting might be a relevant therapeutic strategy in primary SS, possibly enhancing clinical efficacy and safety. ER -